Abstract

Genetic instability is a hallmark during cancer development, such that gene fusions frequently occur when chromosomal translocation joins different genes. A variety of gene fusions have been identified in cancer, some of them are well known biomarkers for cancer diagnostic or chemotherapy targets. Our preliminary study uncovered novel gene fusions joining type I and II keratins in oral squamous cell carcinoma (OSCC) by pair-end RNA-seq transcriptome study. This finding was further validated by dual-color FISH and Sanger sequencing following nested PCR. Keratins form imtermediate filaments in a cell with equal-molar pairing of type I and II keratins, which maintain cell integrity under mechanical stresses and regulate adhesion and migration activity. Although keratins have been known as biomarkers in different types of squamous cell carcinoma (SCC), their functions in cancer development remain controversial. Interestingly, we detected the presence of keratin fusion in early-stage cancer specimens, suggesting the involvement of keratin fusion in carcinogenesis. Although sample size was limited, we found the presence of some keratin fusion variants exclusive to late-stage cancer specimens, which suggest the correlation of keratin fusion with cancer development. Besides OSCC, we also identified keratin fusion in esophageal, nasopharyngeal and cervical carcinoma in our preliminary study, which may suggest keratin fusion as a common driving mechanism among SCCs.